ReviewRegulation of memory - From the adrenal medulla to liver to astrocytes to neurons

- Learning and memory are regulated in part by epinephrine (EPI) responses to experience.
- EPI does not readily enter the brain but controls energy substrates available for brain function.
- EPI initiates increase in blood glucose, which acts centrally to enhance memory.
- Glucose acts centrally to generate lactate in support of memory processing.
- Regulating memory involves integrative physiology of many organ systems besides brain.

Epinephrine, released into blood from the adrenal medulla in response to arousing experiences, is a potent enhancer of learning and memory processing. This review examines mechanisms by which epinephrine exerts its effects on these cognitive functions. Because epinephrine is largely blocked from moving from blood to brain, it is likely that the hormone's effects on memory are mediated by peripheral actions. A classic effect of epinephrine is to act at the liver to break down glycogen stores, resulting in increased blood glucose levels. The increase in blood glucose provides additional energy substrates to the brain to buttress the processes needed for an experience to be learned and remembered. In part, it appears that the increased glucose may act in the brain in a manner akin to that evident in the liver, engaging glycogenolysis in astrocytes to provide an energy substrate, in this case lactate, to augment neuronal functions. Together, the findings reveal a mechanism underlying modulation of memory that integrates the physiological functions of multiple organ systems to support brain processes.This article is part of a Special Issue entitled 'Memory enhancement'.